Sodium Methoxide → 3-[3-(4-Fluorophenyl)(1h-indazol-5-yl)]-5-(pyrrolidinylmethyl)-1h-1,2,4-triazole

HRID 2183335Notes

Reaction equation

HRID 2183335 reaction equation
Cl.C(O[C:5]([C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][N:11]=[C:10]2[C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)=[NH:6])C.NNC([CH:27]1[CH2:31][CH2:30][CH2:29][NH:28]1)=O.C[O-].[Na+].O=[C:36]1[CH:40]=C[N:38]=[N:37]1>CO>[F:22][C:19]1[CH:18]=[CH:17][C:16]([C:10]2[C:9]3[C:13](=[CH:14][CH:15]=[C:7]([C:5]4[N:6]=[C:36]([CH2:40][N:28]5[CH2:27][CH2:31][CH2:30][CH2:29]5)[NH:37][N:38]=4)[CH:8]=3)[NH:12][N:11]=2)=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 10942334Sodium MethoxideHCID 11513733PyrazoloneHCID 14045869Pyrrolidine-2-carbohydrazideHCID 22479739ethoxy[3-(4fluorophenyl)(1H-indazol-5-yl)]methanimine hydrochloride

Product 1

HCID 100215353-[3-(4-Fluorophenyl)(1h-indazol-5-yl)]-5-(pyrrolidinylmethyl)-1h-1,2,4-triazoleYield 5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A suspension of ethoxy[3-(4-fluorophenyl)(1H-indazol-5-yl)]methanimine hydrochloride (0.500 g, 1.56 mmol) and N-aminopyrrolidin-2-ylcarboxamide (0.606 g, 4.69 mmol) in 4 mL of anhydrous methanol was prepared. An excess of a commercial solution of sodium methoxide in methanol (0.727 mL, 4.37 M) was added. After 2 h, the temperature was raised to reflux and was maintained for 48 hours. The analysis of the mixture showed the formation of the corresponding oxodiazole occurring as a side reaction. The reaction was then quenched with water, the pH adjusted to neutral and the crude product extracted with ethyl acetate. The title compound was purified by preparative HPLC (0.030 g, 5% yield): 1H NMR (CD3OD) δ 8.69 (t, 1H), 8.10-8.02 (m, 3H), 7.68 (d, 1H), 7.05 (t, 2H), 4.52 (t, 1H), 3.17 (m, 2H), 2.39-1.99 (m, 4H), 2.37 (s, 6H), 2.30 (s, 2H), 1.12 (s, 9H); ES-MS (m/z) 349 [M+H]+.

Workup

  1. customwas prepared
  2. temperaturethe temperature was raised
  3. temperatureto reflux
  4. temperaturewas maintained for 48 hours
  5. customas a side reaction
  6. customThe reaction was then quenched with water
  7. extractionextracted with ethyl acetate
  8. customThe title compound was purified by preparative HPLC (0.030 g, 5% yield)

Sources & evidence

ORD record
ord-d71f666510594bee966ef90d0b67d83e
Source dataset
uspto-grants-2005_05
Patent number
US06897231B2

Reaction notes

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